rs754405771

Variant names:

• chr9-70113084-A-C
• rs754405771
• NM_153267.5:c.595A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-70113084-A-C
• chr9-70113084-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153267.5(MAMDC2):​c.595A>C​(p.Asn199His) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N199D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAMDC2 NM_153267.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83
• Publications: 0 publications found

Genes affected

MAMDC2 (HGNC:23673): (MAM domain containing 2) Predicted to enable glycosaminoglycan binding activity. Predicted to act upstream of or within peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

MAMDC2-AS1 (HGNC:48719): (MAMDC2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAMDC2	NM_153267.5	c.595A>C	p.Asn199His	missense_variant	Exon 5 of 14	ENST00000377182.5	NP_694999.3
MAMDC2	NM_001347990.2	c.595A>C	p.Asn199His	missense_variant	Exon 5 of 12		NP_001334919.1
MAMDC2	NR_125850.1	n.1212A>C		non_coding_transcript_exon_variant	Exon 5 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAMDC2	ENST00000377182.5	c.595A>C	p.Asn199His	missense_variant	Exon 5 of 14	1	NM_153267.5	ENSP00000366387.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461786 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0079	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.8
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.18
Sift	Benign	0.034	D
Sift4G	Benign	0.084	T
Polyphen		0.81	P
Vest4		0.48
MutPred		0.62		Gain of disorder (P = 0.0555);
MVP		0.39
MPC		0.35
ClinPred		0.66	D
GERP RS		5.7
Varity_R		0.30
gMVP		0.51
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs754405771; hg19: chr9-72728000;